Clonidine is a centrally-acting alpha-agonist used clinically to control hypertension. We have shown that clonidine decreases MOPEC-SO4, a metabolite of norepinephrine, levels in the brain. This indicates that clonidine decreases turnover or synthesis of norepinephrine which should be reflected in changes in tyrosine hydroxylase activity. We previously found that acute or chronic treatment of spontaneously hypertensive rats (SHR) with clonidine does not affect the apparent Km of tyrosine hydroxylase for the synthetic cofactor, 6-methyltetra-hydropterine, when measured in vitro in several different brain regions. Wistar-Kyoto (WKY) rats were acutely treated with clonidine and tyrosine hydroxylase activity was measured in forebrain, hippocampus, hypothalamus, pons-medulla and striatum. Clonidine caused a small, but significant increase in the Km and Vmax for cofactor in the forebrain. Tyrosine hydroxylase activity was unaffected in the other brain regions. Clonidine withdrawal after ten days of treatment caused a sustained increase in the Vmax of tyrosine hyroxylase from the pons-medulla.